Viral protein

Last updated: 2022 Jul 13
Total hit(s): 52
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Mass spectrometry and kinetic studies have showed that Oridonin binds at the SARS-CoV-2 3CLpro catalytic site by forming a C-S covalent bond and blocks substrate binding through a nonpeptidomimetic covalent binding mode. TSA assay identified SAA (Salvianolic acid A ), EGCG (Epigallocatechin gallate), and Oridonin as potential 3CLpro inhibitors. Oridonin blocks the infectivity of SARS-CoV-2 in Vero E6 cell-based experiments. Solving the co-crystal structure of the 3CLpro-Oridonin complex revealed that Oridonin binds at the 3CLpro catalytic site by forming a CS covalent bond, and blocks substrate binding.
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 		35600064
()
PMID
35600064
Title Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease
Impact factor
N/A
Date of Entry 2022 Jul 13

In-vitro biochemical assays show that Nirmatrelvir inhibited wildtype Mpro with a mean Ki of 0.93 nM and the mutated enzymes containing the K90R (Alpha, Beta, Gamma variants) with a Ki 1.05nM, G15S (Lambda variant) with Ki 4.07 nM and P132H (Omicron) with a Ki 0.64 nM. The in-vitro findings imply that PAXLOVID has the ability to sustain plasma nirmatrelvir concentrations several times higher than those required to prevent SARS-CoV-2 VOC/VOI, including Omicron, from multiplying in cells.
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 		Pre-print (bioRxiv)
PMID
~
Title Structural basis for Nirmatrelvir in vitro efficacy against SARS-CoV-2 variants
Impact factor
N/A
Date of Entry 2022 Mar 11

The molecular interaction (MI) energy values between the Omicron Spike protein-RBD and ACE2 is 749.8 kcal.mol-1. This is 1.4 times delta variant MI (538.1) and 2.7 times alpha variant MI (276.9). The strong interaction can be contributed to mutations to lysine (K) at N440K, T478K and Q493K in the Omicron variant, which bind to the contact site acidic amino acids of ACE2. Covid-19 variants transmissible strength can be contributed by basic amino acids, especially lysine. Basic amino acids at the interaction site of S-RBD increased the binding affinity with ACE-2.
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 		35026638
(Talanta)
PMID
35026638
Date of Publishing: 2022 Apr 1
Title Quantitative in silico analysis of SARS-CoV-2 S-RBD omicron mutant transmissibility
Author(s) name Hanai T.
Journal Talanta
Impact factor
10.5
Citation count: 5
Date of Entry 2022 Feb 23

The K417N mutation of Omicron reduces ACE2 binding affinity, but new mutations Q493R, G496S and Q498R, have a compensatory effect on the strength of ACE2 binding and hence Omicron has similar binding affinities of Delta variant. The Omicron spike protein exhibits a measurable increase in affinity for ACE2 relative to the ancestral Wuhan strain, the ACE2 affinity is similar for Delta and Omicron variants.
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 		Pre-print (bioRXiv)
Title SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion
Impact factor
N/A
Date of Entry 2022 Jan 10

The RBD of 2019-nCoV S protein binds with human ACE2 with an affinity (KD) 15.2nM which is similar to SARS-CoV and ACE2 binding affinity of 15nM. The RBD of 2019-nCoV is different to that of SARS-CoV. But this did not result in any change with its interaction with ACE2 receptor but had an impact on the cross-reactivity of neutralizing antibodies.
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 		32065055
(Emerg Microbes Infect)
PMID
32065055
Date of Publishing: 2020
Title Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody
Author(s) nameTian X, Li C et al.
Journal Emerg Microbes Infect
Impact factor
5.84
Citation count: 655
Date of Entry 2021 Nov 20

SARS-CoV-2 RBD interacts with the N-linked glycan on Asn90 of ACE2 which is absent in SARS-CoV-1.MD simulation of SARS-CoV-2 with ACE2 indicate unbinding forces range from 70 to 105pN and removal of the N-linked glycan reduced unbinding forces to 50-70pN The difference in ACE2 binding between SARS-CoV-2 and SARS-CoV-1 and could help develop new strategies to block SARS-CoV-2 entry.
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 		32766576
(bioRxiv)
PMID
32766576
Date of Publishing: 2020 Jul 31
Title Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction
Author(s) nameCao W, Dong C et al.
Journal bioRxiv
Impact factor
- n/a -
Citation count: 1
Date of Entry 2021 Oct 30

MD simulation of the glycosylated trimer spike of SARS-CoV-2 in complex with glycosylated, soluble, human ACE 2 reveals that glycan at N546 of ACE2 interacts with N0074 and N0165 in the S protein. To develop ACE2 as a possible decoy therapy, understanding the influence of ACE2 polymorphisms on glycosylation and S binding is crucial.Modifications of ACE2 glycosylation could lead to more potent biologics that are more competitive inhibitors of S binding.The study provides a foundation for the development of immunogens, vaccines, antibodies, and inhibitors, as well as new information on the mechanisms that allow for glycan microheterogeneity.In order to produce treatments, detailed investigations of the influence of new polymorphisms in S and natural and designed-for-biologics variants of ACE2 on glycosylation and binding properties are necessary.
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 		32743578
(bioRxiv)
PMID
32743578
Date of Publishing: 2020 Jul 24
Title Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor
Author(s) nameZhao P, Praissman JL et al.
Journal bioRxiv
Impact factor
- n/a -
Citation count: 1
Date of Entry 2021 Oct 30

The high-resolution structure of a ternary complex of SARS-CoV-2 nsp16 and nsp10 in the presence of cognate RNA substrate analogue and methyl donor, S-adenosyl methionine (SAM) shows conformational changes associated with substrate binding as the enzyme transitions from a binary to a ternary state. ~
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 		32709886
(Nat Commun)
PMID
32709886
Date of Publishing: 2020 Jul 24
Title Structural basis of RNA cap modification by SARS-CoV-2
Author(s) nameViswanathan T, Arya S et al.
Journal Nat Commun
Impact factor
11.8
Citation count: 92
Date of Entry 2021 Oct 27

Molecular interaction studies of SARS-CoV-2 RBD with different variants of hACE2. No major divergence of the interaction interface of SARS-CoV-2 RBD with hACE2
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 		32410735
(Biochem Biophys Res Commun)
PMID
32410735
Date of Publishing: 2020 Jun 30
Title Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS -Cov , hot-spot analysis and effect of the receptor polymorphism
Author(s) nameOthman H, Bouslama Z et al.
Journal Biochem Biophys Res Commun
Impact factor
2.73
Citation count: 69
Date of Entry 2021 Aug 2

Heparin binding accelerates the aggregation of pathological amyloid proteins in the brain. Comparative study to the docking score of SARS-CoV-2 S1-heparin complex to amyloid forming proteins shows molecular interaction of the SARS-COV-2 Spike S1 RBD and Heparin shows a high docking score of -282.57. By targeting the binding and aggregation process of the S1 and Heparin, neurodegenration can be prevented.
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 		33789211
(Biochem Biophys Res Commun)
PMID
33789211
Date of Publishing: 2021 May 21
Title SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration
Author(s) name Idrees D, Kumar V.
Journal Biochem Biophys Res Commun
Impact factor
2.73
Citation count: 18
Date of Entry 2021 Aug 12

SARS-CoV-2 S1 RBD binds heparin binding proteins including A, -synuclein, tau, prion, and TDP-43 RRM. The heparin binding site of S1 protein assists the binding to amyloid proteins to the viral surface and initate aggregation of these proteins, leading to neurodegenration in brain. This provides a reasonable explanation for the neurodegenerative distresses caused by a COVID infection. Increase in Kd as the temperature increased from 25 C to 40 C, showed a decrease in binding affinity for SARS-CoV-2 S1 protein complexes.
Increase in temperature usually disrupts the noncovalent interactions between a protein-protein complex, but, the decrease in binding affinity across the temperatures was less apparent for the -Syn complex with S1. This anomaly suggests a stable interaction between -synuclein to SARS-CoV-2 S1 protein.
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 		33789211
(Biochem Biophys Res Commun)
PMID
33789211
Date of Publishing: 2021 May 21
Title SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration
Author(s) name Idrees D, Kumar V.
Journal Biochem Biophys Res Commun
Impact factor
2.73
Citation count: 18
Date of Entry 2021 Aug 12

Based on the intermolecular contact maps (COCOMAPS tool) of ACE2-S complex structure, three short peptides (pep1c, pep1d, pep1e) were designed to block virus-host interaction in the early stages of SARS-CoV-2 infection. New therapeutics for oral administration against SARS-CoV-2 infection can be developed using these peptides, which could be an alternative to traditional drug development.
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 		33918595
(Molecules)
PMID
33918595
Date of Publishing: 2021 Apr 9
Title Native Structure-Based Peptides as Potential ProteinProtein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor
Author(s) nameOdolczyk N, Marzec E et al.
Journal Molecules
Impact factor
3.01
Citation count: 8
Date of Entry 2021 Aug 12

The study compares the similarities and differences in the structure of heparin sulfate (HS) in human and bat lungs. Also, discusses about the binding capacity of spike protein of SARS-CoV-2 with homosapiens and chiroptera's lung heparin sulfate. The spike glycoprotein of COVID 19 binds 3.5 times stronger to the human lung heparin(HS) sulfate than bat lung heparin sulfate. The molecular weight of the heparin sulfate is more important than the sulfation level for lung HS binding to SARS-CoV-2 virus spike protein.
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 		33712145
(Carbohydr Polym)
PMID
33712145
Date of Publishing: 2021 May 15
Title Heparan sulfates from bat and human lung and their binding to the spike protein of SARS-CoV-2 virus
Author(s) nameYan L, Song Y et al.
Journal Carbohydr Polym
Impact factor
6.23
Citation count: 13
Date of Entry 2021 Aug 11

Molecular interaction studies of SARS-CoV-2 RBD with different variants of hACE2. No major divergence of the interaction interface of SARS-CoV-2 RBD with hACE2
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 		PMC
Title Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS -Cov , hot-spot analysis and effect of the receptor polymorphism
Impact factor
N/A
Date of Entry 2021 Jul 28

Molecular interaction studies of RBD from SARS-CoV-2 and SARS-CoV with different ACE2 orthologues Q493 might be responsible for higher affinity due to a better satisfaction of the Van der Waals by the longer polar side chain of asparagine.
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 		32410735
(Biochem Biophys Res Commun)
PMID
32410735
Date of Publishing: 2020 Jun 30
Title Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS -Cov , hot-spot analysis and effect of the receptor polymorphism
Author(s) nameOthman H, Bouslama Z et al.
Journal Biochem Biophys Res Commun
Impact factor
2.73
Citation count: 69
Date of Entry 2021 Jul 28

Molecular interaction studies of SARS-CoV-2 RBD with different variants of hACE2. No major divergence of the interaction interface of SARS-CoV-2 RBD with hACE2
✍
 		PMC
Title Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS -Cov , hot-spot analysis and effect of the receptor polymorphism
Impact factor
N/A
Date of Entry 2021 Jul 28

Molecular interaction study between polymorphic spike protein and human ACE2 reveals affinity and stability of ACE2 to spike protein of SARS-CoV-2 for a mutants I468V, N638S, R708Q is -65.09 kcal/mol, -65.09kcal/mol and -64.99 kcal/mol, respectively. The variants in the spike protein of SARS-CoV-2 and hACE2 would provide a database for tracking the adaptive mutation of SARS-CoV-2 and potential recombination events across different species.
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 		33542420
(Sci Rep)
PMID
33542420
Date of Publishing: 2021 Feb 4
Title Dynamics of binding ability prediction between spike protein and human ACE2 reveals the adaptive strategy of SARS-CoV-2 in humans
Author(s) nameXue X, Shi J et al.
Journal Sci Rep
Impact factor
4.12
Citation count: 6
Date of Entry 2021 Jul 28

Cross-reactivity of B6 monoclonal antibody with the spike glycoproteins of SARS-CoV-2, SARS-COV, MERS and HKU4 is because of the strict conservation of 3 of the 4 hydrophobic residues in the stem helix except for the substitution of F1238MERS-CoV with Y1137SARS-CoV/Y1155SARS-CoV-2 or W1240 OC43/W1237HKU1. B6 binding sterically interferes with S fusogenic conformational changes and blocks viral entry through inhibition of membrane fusion
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 		33981021
(Nat Struct Mol Biol)
PMID
33981021
Date of Publishing: 2021 May 12
Title Structural basis for broad coronavirus neutralization
Author(s) nameSauer MM, Tortorici MA et al.
Journal Nat Struct Mol Biol
Impact factor
9.8
Citation count: 46
Date of Entry 2021 Jul 28

Host protein arginine methyltransferases (PRMTs) methylates SARS-CoV-2 N protein at residues R95 and R177 within RGG/RG motifs.Type I PRMT inhibitor (MS023) or substitution of R95 or R177 with lysine inhibits interaction of N protein with the 5-UTR of SARS-CoV-2 genomic RNA, a property required for viral packaging. Type I PRMT inhibitors (MS023), cancer drug canditates, have found to reduce SARS-CoV-2 production by inhibiting the methylation of arginine in the N protein of SARS-CoV-2 and hence are promising antivirals.
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 		34029587
(J Biol Chem)
PMID
34029587
Date of Publishing: 2021 May 23
Title Arginine methylation of SARS-Cov-2 nucleocapsid protein regulates RNA binding, its ability to suppress stress granule formation, and viral replication
Author(s) nameCai T, Yu Z et al.
Journal J Biol Chem
Impact factor
3.96
Citation count: 11
Date of Entry 2021 Jul 28

Surface plasmon resonance (SPR) was used to compare the kinetics of SARS-CoV-2 S protein both D614 and D614G binding to human ACE2. D614G decreases the affinity for ACE2 by increasing the rate of dissociation. The increased infectivity of D614G is not explained by greater ACE2 binding strength.
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 		32991842
(Cell)
PMID
32991842
Date of Publishing: 2020 Oct 29
Title Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant
Author(s) nameYurkovetskiy L, Wang X et al.
Journal Cell
Impact factor
27.35
Citation count: 434
Date of Entry 2021 Jun 15

Complex of ACE2 receptor and N501Y spike protein ectodomains shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2 providing a structural explanation for the increased ACE2 affinity of the N501Y mutant, and its increased infectivity, but the mutation does note cause large structural changes. Structural studies establish the molecular basis showing the increase in ACE2 binding efficiency conferred by the N501Y mutation. Despite the higher infectivity of SARS-CoV-2 viruses carrying the N501Y mutation, the availability of the extended epitope surface on the RBD enables effective neutralization by VH ab8 and Fab ab1.
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 		33914735
(PLoS Biol)
PMID
33914735
Date of Publishing: 2021 Apr 29
Title Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies
Author(s) nameZhu X, Mannar D et al.
Journal PLoS Biol
Impact factor
7.62
Citation count: 68

SARS-CoV-2 receptor-binding domain (RBD) binds to human ACE2 receptor (hACE2) more strongly than that of bat ACE2 2 from Rhinolophus macrotis (bACE2-Rm). Glycosylation modification in bACE2-Rm doesn't influence the binding of SARS-CoV-2 RBD with bACE2-Rm.ns.
Patch 2 interaction in bACE2-Rm and hACE2 was highly conserved compared to Patch 1 interaction which showed significant differences in both.
In bACE2-Rm, residues Y41 and E42 are significant within the interface of SARS-CoV-2 RBD, whereas the residues in human include Y41 and Q42.
Most of the residues involved in ACE2 homodimer formation were conserved in both human and bats, indicating possible conservation of ACE2 dimer attributes during evolution.
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 		33335073
(Proc Natl Acad Sci U S A)
PMID
33335073
Date of Publishing: 2021 Jan 5
Title Cross-species recognition of SARS-CoV-2 to bat ACE2
Author(s) nameLiu K, Tan S et al.
Journal Proc Natl Acad Sci U S A
Impact factor
9.35
Citation count: 23

Molecular docking experiments with ORF7a and the LFA-1 and Mac-1 I domains reveal E26 (Glu26) in SARS-CoV2 ORF7a forms hydrogen bonds with L205 in LFA-1 and R208 in Mac-1 and thereby interaction between SARS-CoV-2 and leukocytes could result in a modified immune response. ORF7a-mediated effects on immune cells such as T lymphocytes and macrophages (leukocytes) could help understand the disease further and develop effective treatments.
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 		33305306
(Biosci Rep)
PMID
33305306
Date of Publishing: 2020 Dec 11
Title Structural assessment of SARS-CoV2 accessory protein ORF7a predicts LFA-1 and Mac-1 binding potential
Author(s) nameNizamudeen ZA, Xu ER et al.
Journal Biosci Rep
Impact factor
2.51
Citation count: 7

Nsp13-1 stabilizes SARS-CoV-2 replication and transcription (RTC) complex by contacting with nsp13-2, which anchors the 5'-extension of RNA template, and interacting with nsp7-nsp8-nsp12-RNA. Different orientations of nsp13-1 results in different interactions with the two forms of mini RTC. Mini RTC with an nsp12R365A mutation has greater helicase activity compared to individual apsnsp13. Nsp13-1T216A mutation has a decreased helicase activity.
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 		33208736
(Nat Commun)
PMID
33208736
Date of Publishing: 2020 Nov 18
Title Architecture of a SARS-CoV-2 mini replication and transcription complex
Author(s) nameYan L, Zhang Y et al.
Journal Nat Commun
Impact factor
11.8
Citation count: 61

Structural characterization of SARS-CoV-2 spike glycoprotein (RBD to S2 double mutant (rS2d)) constructs. And determing its binding with the antibody CR3022 and human cell receptor ACE2. The spike glycoprotein mutant constructs (rS2d) with double mutation S383C, D985C were developed. The RBD in the rS2d construct is locked in the 'down ' state conformation.
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 		32699321
(Nat Struct Mol Biol)
PMID
32699321
Date of Publishing: 2020 Oct
Title Controlling the SARS-CoV-2 spike glycoprotein conformation
Author(s) nameHenderson R, Edwards RJ et al.
Journal Nat Struct Mol Biol
Impact factor
9.8
Citation count: 150